In addition, several studies have confirmed that markers of low-grade metabolic acidosis, such as lower plasma bicarbonate [6, 15, 16], higher anion gap [15], lower urine pH [47] and high levels of plasma lactate [48], are linked to insulin resistance, suggesting that low-grade metabolic acidosis could be involved in the aetiology of type 2 diabetes. This evidence concerns the gene INS and type 2 diabetes mellitus.